Prostacyclin (I, PGI.sub.2), first discovered in 1976, is one of the most potent natural inhibitors of blood platelet aggregation. (See S. Moncado et al., Nature, 263, 663 (1976) and R. Johnson et al., Prostaglandins, 12, 915 (1976)). Unfortunately, its low metabolic stability due to enol ether hydrolysis greatly diminished its pharmacological utility. Major interest of late has focused on the synthesis of more stable analogs, such as the benzoprostacyclins Ia-c, described by K. Ohno et al. in U.S. Pat. No. 4,301,164. ##STR1## These compounds similarly exhibit substantial inhibition of platelet aggregation.
Present synthetic approaches to the benzoprostacyclins are very lengthy and rather inefficient. For example, the synthesis of compound Ia as reported by H. Nagase et al., Tetrahedron Lett., 31, 4493 (1990) requires 23 steps. As reported by K. Ohno et al. in U.S. Pat. No. 4,474,802, the synthesis of the C.sub.1 -methyl ester of Ib requires at least 17 steps.
Therefore, a need exists for efficient methods to synthesize benzoprostacyclins.